Carbohydrates and Lipids - Lecture Notes

Carbohydrates and Lipids Dr Nick Hopcroft Academic Lead for Cell and Tissue Biomedicine [email protected]  Learning Outcomes Major roles of carbohydrates and lipids Chemical structures of carbohydrates Chemical structures of lipids Relationship betw...

Carbohydrates and Lipids Dr Nick Hopcroft Academic Lead for Cell and Tissue Biomedicine [email protected]  Learning Outcomes Major roles of carbohydrates and lipids Chemical structures of carbohydrates Chemical structures of lipids Relationship between chemical composition and energy content Composition and physiological roles of lipoproteins Glucose transporter proteins  Biological Macromolecules Macromolecules are large molecules – organic (carbon-containing) macromolecules are crucial for most biological functions: Nucleic acids: Information storage / transmission (DNA and RNA) Proteins: Enzymatic catalysis Antibodies Hormonal signalling Structural proteins Contractile proteins Gas transport Carbohydrates: Energy source Lipids (Fats): Energy source Membrane components Hormonal signalling  Carbohydrates Carbohydrates have the general molecular formula [C(H2O)]n (‘hydrated carbon’), with n≥3 generally accepted as a condition They are classified according to the number of monomers: Monosaccharides (1 monomeric unit) Disaccharides (2 monomeric units) Oligosaccharides (3-10 monomeric units) Polysaccharides (>10 monomeric units) Most carbohydrates in a typical healthy human diet are polysaccharides (‘complex carbohydrates’; e.g. starch), which need to be broken down in order to be absorbed  Monosaccharides Monosaccharides have names ending ‘-ose’ and can be classified by chemical structure in complementary ways: Number of carbon atoms: triose (3), tetrose (4) pentose (5), (size) hexose (6) Isomer: These contain the same atoms, but bonded to each other in a different 3D arrangement Ketone vs. Aldehyde (dihydroxyaceto (glyceraldehyd ne) e)  Monosaccharides Monosaccharides have names ending ‘-ose’ and can be classified by chemical structure in complementary ways: Number of carbon atoms: triose (3), tetrose (4) pentose (5), (size) hexose (6) Isomer: These contain the same atoms, but bonded to each other in a different 3D arrangement D-isomer vs. L-isomer (D- (L- glyceraldehyde) glyceraldehyd e) Glucose, fructose and galactose are all hexoses with different arrangements of the same atoms  Monosaccharide Cyclisation Longer-chain monosaccharides (pentoses, hexoses) form cyclic molecules: Ribose or Glucose or Pentoses normally form 5-membered rings and hexoses 6- membered rings, but this is not necessarily the case – oxygen is also part of the ring  Important Monosaccharides Trioses: dihydroxyacetone phosphate and glyceraldehyde-3- phosphate are important intermediates in energy metabolism Pentoses: ribose and deoxyribose are crucial components of RNA and DNA respectively Hexoses: Glucose Galactose Fructose These are found in important disaccharides or oligosaccharides  Important Disaccharides Disaccharides are formed by a reaction between two mono- saccharides, which eliminates water and forms a glycosidic bond Sucrose: Glucose and fructose joined together Lactose: Galactose and glucose joined together Maltose: Two glucoses joined together (breakdown product of starch or glycogen)  Important Poly/Oligosaccharides Starch Obtained in diet from plant sources 75% amylopectin - branched polymer of glucose (formed by α-1,4 and α-1,6 glycosidic bonds) 25% amylose - linear polymer of glucose (formed by α-1,4 glycosidic bonds only) Cellulose Present in diet from plant sources, but not (component digestible by humans due to lack of cellulase of fibre) enzyme; linear polymer of glucose Glycogen Obtained in diet from animal sources; extensively branched polymer of glucose Dextrin Breakdown product of starch and glycogen; branched oligomer of glucose  Lipids The main types of biologically important lipids are: Fatty acids Triglycerides (triacylglycerols) Cholesterol Cholesterol esters  Fatty Acids Fatty acids are hydrocarbon chains of various lengths – considered ‘long chain’ if >12C and ‘very long chain’ if >22C They can be saturated or unsaturated – unsaturated fatty acids have at least one C=C double bond They can be joined to glycerol to form triglycerides +  Fatty Acid Nomenclature There are various naming systems, which are either unsystematic or systematic but not very convenient The most descriptive nomenclature is C#1:#2(Δ#,#...) where #1 is the total number of carbons, #2 is the number of double bonds and the numbers in brackets indicate the carbons at which the double bonds occur, counting from the acidic end The ω-# (‘omega-#’) nomenclature describes the position of the final double bond, counting from the hydrocarbon end  cis vs trans Fatty Acids The cis or trans nomenclature describes a form of isomerism at double bonds (around which there is no rotation) and applies to unsaturated fatty acids Either isomer can be incorporated into triglycerides and modified lipids cis fatty acids pack next to each other less closely than trans ones, so cause membranes to be more fluid Oleic acid = C18:1(Δ9), an ω-9 fatty acid  Modified Lipids Phospholipids consist of a phosphate group attached to one or more fatty acid chains via glycerol or sphingosine, which itself contains a long hydrocarbon chain Glycolipids consist of a carbohydrate element (usually an oligosaccharide) attached to one or more fatty acid chains directly or via glycerol or sphingosine Both are important components of cellular membranes, with the amphipathic (polar/non-polar) nature of phospholipids being integral to membrane structure and glycolipids functioning in cell surface recognition  Ketone Bodies Ketone bodies are small (4-carbon), water-soluble fatty acids formed by the liver during fasting, when they become important energy substrates for the brain Acetoacetic acid, β-hydroxybutyric acid and the breakdown product acetone are the main ketone bodies Acetoacetic β-hydroxybutyric acid acid In Type 1 diabetes, excessive formation of ketone bodies by the liver can result in dangerously high concentrations in the blood  Roles of Lipids Fuels (substrates for energy metabolism) for cells e.g. fatty acids, ketone bodies Energy storage, e.g. triglycerides Transport between tissues, e.g. cholesterol esters, triglycerides Structural components of cell membranes, e.g. phospholipids, cholesterol Chemical messengers, e.g. steroids, diglycerides  Energy Release Energy is released from organic molecules by oxidation reactions Oxidation can involve literally adding oxygen atoms (‘oxygenation’), but this isn’t always the case Oxidation is the loss of electrons The opposite to oxidation is reduction, which is the gain of electrons Oxidation applies to inorganic chemical species too, e.g. Fe3+ is more oxidised than Fe2+ For organic molecules, the more carbon/hydrogen and less oxygen they contain, the more scope there is for oxidising them  Lipoproteins Lipids are transported through aqueous environments such as blood plasma in complex structures called lipoproteins Lipoproteins have a hydrophobic core containing triglycerides and cholesterol esters and a hydrophilic surface consisting of phospholipids, free cholesterol and proteins (apolipoproteins) They can be separated by ultracentrifugation and classified according to their densities Lipoprotein lipase releases fatty acids from chylomicrons and VLDLs into the tissues Lipoproteins Composition Main function Highest triglycerides Deliver dietary Lowest cholesterol (exogenous) triglycerides to peripheral tissues High triglycerides Deliver endogenous Low cholesterol triglycerides to peripheral tissues Low triglycerides Deliver cholesterol Highest cholesterol to peripheral tissues and to liver Lowest triglycerides Deliver cholesterol High cholesterol from peripheral tissues to the liver for elimination  Lipoprotein Transport Biliary Dietar cholesterol HDL y Extra-hepatic lipids tissues Liver LDL Remnan Chylomicro ts VLDL IDL ns Lipoprotein Lipoprotein lipase lipase  Lipoprotein Transport Biliary Dietar cholesterol y lipids Liver Exogenous lipid cycle Remnan Chylomicro ts ns Lipoprotein lipase  Lipoprotein Transport HDL Extra-hepatic tissues Liver Endogenous LDL lipid cycle VLDL IDL Lipoprotein lipase  Glucose Transporters Transporter Affinity Specificity Tissue Comments Km (mM) distribution Passive transport GLUT-1 1.5 Glucose, RBCs, brain, Basal uptake galactose, ubiquitous (high mannose affinity) GLUT-2 15.0 Glucose, Liver, Glucose fructose pancreatic -cell sensing (low affinity) GLUT-3 1.8 Glucose Brain, intestine, placenta GLUT-4 5.0 Glucose Muscle (Sk, Insulin Card), sensitive adipose GLUT-5 10.0 Fructose Intestine Secondary active transport SGLT-1 0.3 2 glucose, Intestine Na+, Kidney galactose  Insulin Sensitivity of GLUTs Not Insulin sensitive Insulin sensitive glucose uptake Insulin sensitive glucose GLUT 2 uptake NOT insulin sensitive transport GLUT NOT 2 insulin- sensitive Pancreatic β-cell  Recommended Reading Medical Sciences, Naish and Syndercombe Court Chapter 2, pages 22-26 in particular